Electrocatalytic hydrogenation of cyanoarenes, nitroarenes, quinolines, and pyridines under mild conditions with a proton-exchange membrane reactor

• Koichi Mitsudo,
• Atsushi Osaki,
• Haruka Inoue,
• Eisuke Sato,
• Naoki Shida,
• Mahito Atobe and
• Seiji Suga

Beilstein J. Org. Chem. 2024, 20, 1560–1571, doi:10.3762/bjoc.20.139

• reactions. As PEM reactors are flow reactors, they have an advantage over batch reactors in terms of continuous production. Several reductive transformations taking advantage of the characteristics of the PEM reactor have been reported in recent years. For example, Atobe et al. reported the electrocatalytic

Benzylic C(sp³)–H fluorination

• Alexander P. Atkins,
• Alice C. Dean and
• Alastair J. J. Lennox

Beilstein J. Org. Chem. 2024, 20, 1527–1547, doi:10.3762/bjoc.20.137

• continuous flow system (Figure 26) [71]. The authors were able to demonstrate rapid benzylic fluorination of 13 substrates, requiring residence times below 30 min. The use of photoexcited aryl ketones was further expanded in 2016 by Lectka and co-workers who reported the use of 5-dibenzosuberenone as a

• fluorination in continuous flow. Photochemical phenylalanine fluorination in peptides. Decatungstate-photocatalyzed versus AIBN-initiated selective benzylic fluorination. Benzylic fluorination using organic dye Acr+-Mes and Selectfluor. Palladium-catalysed benzylic C(sp3)–H fluorination with nucleophilic

Photoswitchable glycoligands targeting Pseudomonas aeruginosa LecA

• Yu Fan,
• Ahmed El Rhaz,
• Stéphane Maisonneuve,
• Emilie Gillon,
• Maha Fatthalla,
• Franck Le Bideau,
• Guillaume Laurent,
• Samir Messaoudi,
• Anne Imberty and
• Juan Xie

Beilstein J. Org. Chem. 2024, 20, 1486–1496, doi:10.3762/bjoc.20.132

• continuous irradiation Hg/Xe lamp (Hamamatsu, LC6- or LC8-Lightningcure, 200 W) equipped with narrow band interference filters of appropriate wavelengths: Semrock BP-370/36 for λirr = 370 nm, Semrock FF01-438/24-25 for λirr = 438 nm, Semrock FF01-485/20-25 for λirr = 485 nm. The irradiation power was

Light on the sustainable preparation of aryl-cored dibromides

• Fabrizio Roncaglia,
• Alberto Ughetti,
• Nicola Porcelli,
• Biagio Anderlini,
• Andrea Severini and
• Luca Rigamonti

Beilstein J. Org. Chem. 2024, 20, 1076–1087, doi:10.3762/bjoc.20.95

• %) was also included. Under these conditions, a first assessment of the reaction time was performed (entries 1, 2, 3 of Table 2), resulting in the predominant ring monobromination, even after 48 h. Considering the continuous conversion of HBr into Br2 by means of the peroxide, we speculated on the

Carbonylative synthesis and functionalization of indoles

• Alex De Salvo,
• Raffaella Mancuso and
• Xiao-Feng Wu

Beilstein J. Org. Chem. 2024, 20, 973–1000, doi:10.3762/bjoc.20.87

• indolo[1,2-c]quinazolin-6(5H)-one derivatives. Finally, starting from 1,2-bis(2-nitrophenyl)ethene and 1-methoxy-2-nitro-3-(2-nitrostyryl)benzene the related indolo[3,2-b]indoles were not observed (Scheme 17). One year later, by using continuous flow technology, Gutmann, Kappe and colleagues developed a

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

Advancements in hydrochlorination of alkenes

• Daniel S. Müller

Beilstein J. Org. Chem. 2024, 20, 787–814, doi:10.3762/bjoc.20.72

• 1990s when Kropp's pivotal paper on the surface-mediated hydrochlorination of unactivated alkenes reignited interest [10]. Since then, continuous efforts have been made to enhance the generality, efficiency, and functional group tolerance of hydrochlorination reactions. Recently, several groups reported

A myo-inositol dehydrogenase involved in aminocyclitol biosynthesis of hygromycin A

• Michael O. Akintubosun and
• Melanie A. Higgins

Beilstein J. Org. Chem. 2024, 20, 589–596, doi:10.3762/bjoc.20.51

• , the pellet was resuspended in 40 mL of sucrose solution (25% sucrose, 50 mM Tris pH 8) using continuous stirring. Then, 10 mg of lysozyme (Bio Basic) was added and stirred at room temperature for 10 min, followed by the addition of 80 mL deoxycholate solution (1% deoxycholate, 1% Triton X-100, 100 mM

Synthesis of 2,2-difluoro-1,3-diketone and 2,2-difluoro-1,3-ketoester derivatives using fluorine gas

• Alexander S. Hampton,
• David R. W. Hodgson,
• Graham McDougald,
• Linhua Wang and
• Graham Sandford

Beilstein J. Org. Chem. 2024, 20, 460–469, doi:10.3762/bjoc.20.41

• substrates using fluorine gas has been used successfully for the production of 5-fluorouracil (generic, anticancer) and voriconazole (V-FEND, Pfizer, antifungal) [33]. Methods have been developed for the selective monofluorination of 1,3-dicarbonyl derivatives by fluorine gas using batch and continuous flow

Green and sustainable approaches for the Friedel–Crafts reaction between aldehydes and indoles

• Periklis X. Kolagkis,
• Eirini M. Galathri and
• Christoforos G. Kokotos

Beilstein J. Org. Chem. 2024, 20, 379–426, doi:10.3762/bjoc.20.36

• development of greener synthetic technologies, like photocatalysis, organocatalysis, the use of nanocatalysts, microwave irradiation, ball milling, continuous flow, and many more. Thus, in this review, we summarize the medicinal properties of BIMs and the developed BIM synthetic protocols, utilizing the

• number of inflammatory processes, which can lead to inflammatory bowel disease or Alzheimer’s disease. Therefore, GPR84 agonists are used as medicine for the treatment of various inflammatory diseases, but they have been also linked to the reduction of leukemia cells, since the continuous expression of

Additive-controlled chemoselective inter-/intramolecular hydroamination via electrochemical PCET process

• Kazuhiro Okamoto,
• Naoki Shida and
• Mahito Atobe

Beilstein J. Org. Chem. 2024, 20, 264–271, doi:10.3762/bjoc.20.27

• this case, intramolecular radical trapping by the uracil nucleobase was preferred, leading to the formation of the cyclized alkyl radical D. Continuous radical recombination furnished dimer 4. Conclusion We observed additive-controlled inter- and intramolecular chemoselectivity in the hydroamination of

Copper-catalyzed multicomponent reaction of β-trifluoromethyl β-diazo esters enabling the synthesis of β-trifluoromethyl N,N-diacyl-β-amino esters

• Youlong Du,
• Haibo Mei,
• Ata Makarem,
• Ramin Javahershenas,
• Vadim A. Soloshonok and
• Jianlin Han

Beilstein J. Org. Chem. 2024, 20, 212–219, doi:10.3762/bjoc.20.21

• reaction of CF3CHN2 with carboxylic acids and acetonitrile via a similar process to afford a series of N-trifluoroethylimides (Scheme 1b) [40][41]. Inspired by these elegant works [31][32][33][34][35][36][37][38][39][40][41] and based on our continuous interest in reactions of fluoroalkyldiazo compounds

Metal-catalyzed coupling/carbonylative cyclizations for accessing dibenzodiazepinones: an expedient route to clozapine and other drugs

• Amina Moutayakine and
• Anthony J. Burke

Beilstein J. Org. Chem. 2024, 20, 193–204, doi:10.3762/bjoc.20.19

• suitable surrogate. Not only that, the use of safer to use surrogates, is important for use in enabling technologies, like continuous flow and microwave-heated reactions. In fact, CO-free aminocarbonylation reactions are well known, and molybdenum hexacarbonyl (Mo(CO)6) is a very useful surrogate having

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• maintained with an accuracy of ±0.2 °C. After the instrument was warmed up for at least 1 h (as experience suggests, after this period the temperature within the instrument remains stable for at least 8–10 h of continuous work) the instrument readings were verified against the quartz standards (α = +21.267

Visible-light-induced radical cascade cyclization: a catalyst-free synthetic approach to trifluoromethylated heterocycles

• Chuan Yang,
• Wei Shi,
• Jian Tian,
• Lin Guo,
• Yating Zhao and
• Wujiong Xia

Beilstein J. Org. Chem. 2024, 20, 118–124, doi:10.3762/bjoc.20.12

• their biological activity and potential applications, continuous efforts have been dedicated to the synthesis of DHPI derivatives. Various synthetic strategies have been explored (Scheme 1), including transition-metal-catalyzed cross-coupling reactions [8][9][10], annulation reaction of carbenoids [11

Optimizing reaction conditions for the light-driven hydrogen evolution in a loop photoreactor

• Pengcheng Li,
• Daniel Kowalczyk,
• Johannes Liessem,
• Mohamed M. Elnagar,
• Dariusz Mitoraj,
• Radim Beranek and
• Dirk Ziegenbalg

Beilstein J. Org. Chem. 2024, 20, 74–91, doi:10.3762/bjoc.20.9

• Supporting Information File 1, Figure S2b), while maintaining a continuous flow of N2 in the headspace through a septum. The resulting suspension exhibited a yellow/greenish color and was subsequently washed with deionized water 3–5 times, followed by drying at 70 °C overnight and grinding. The synthesized

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• opposed to continuous flushing to save solvents, the long ODN syntheses required much longer time although solvent consumption was lower. In the future, if both reducing chemical consumption and shortening synthesis time are intended, microfluidic synthesizers may be considered. The ability to synthesize

Studying specificity in protein–glycosaminoglycan recognition with umbrella sampling

• Mateusz Marcisz,
• Sebastian Anila,
• Margrethe Gaardløs,
• Martin Zacharias and
• Sergey A. Samsonov

Beilstein J. Org. Chem. 2023, 19, 1933–1946, doi:10.3762/bjoc.19.144

• reflect the system's state under particular conditions with explicitly defined reaction coordinate values, the visualization of these continuous data potentially offers a more comprehensive insight into the complexity of the system related to its dynamic behavior within each window. Basic FGF Ligand 1

Charge carrier transport in perylene-based and pyrene-based columnar liquid crystals

• Alessandro L. Alves,
• Simone V. Bernardino,
• Carlos H. Stadtlober,
• Edivandro Girotto,
• Giliandro Farias,
• Rodney M. do Nascimento,
• Sergio F. Curcio,
• Thiago Cazati,
• Marta E. R. Dotto,
• Juliana Eccher,
• Leonardo N. Furini,
• Hugo Gallardo,
• Harald Bock and
• Ivan H. Bechtold

Beilstein J. Org. Chem. 2023, 19, 1755–1765, doi:10.3762/bjoc.19.128

• was collected in continuous mode from 2° to 30° (2θ angle) at specific temperatures during the cooling down to room temperature. The temperature was controlled with a TCU2000-temperature control unit (Anton Paar). The absorbance spectra in solution and in spin-coated films were collected with an Ocean

Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• continuous mentorship that significantly contributed to the success of this research. Funding This work was supported by a JSPS KAKENHI Grant-in-Aid for Early-Career Scientists (No. 22K14791(H.S.)), a JSPS KAKENHI Grant-in-Aid for Transformative Research Areas (No. 22H05125 (H.S.)), a MEXT grant for Leading

Non-noble metal-catalyzed cross-dehydrogenation coupling (CDC) involving ether α-C(sp³)–H to construct C–C bonds

• Hui Yu and
• Feng Xu

Beilstein J. Org. Chem. 2023, 19, 1259–1288, doi:10.3762/bjoc.19.94

• further development. To avoid the prefunctionalization of substrates, Li et al. first pioneered the concept of direct cross-dehydrogenative coupling (CDC) through continuous exploration and discovery [7][13][14][15]. The CDC reaction has flourished due to its versatility and has become an important

• application of this method still limited by sustainability, safety, and cost factors. Therefore, further development to shorten the reaction time, improve the reaction efficiency, and reduce energy consumption in an environmentally friendly, practical, and safe method for CDC will be a continuous process [131

Metal catalyst-free N-allylation/alkylation of imidazole and benzimidazole with Morita–Baylis–Hillman (MBH) alcohols and acetates

• Olfa Mhasni,
• Jalloul Bouajila and
• Farhat Rezgui

Beilstein J. Org. Chem. 2023, 19, 1251–1258, doi:10.3762/bjoc.19.93

• direct amination of MBH alcohols 4a–d, with a poor leaving group (OH). Under the previous conditions (2 equiv of imidazole, toluene, reflux), the conversion of alcohol 4a [28] into the corresponding imidazole 6a was very slow and the starting materials were almost recovered. However, the continuous

Radical ligand transfer: a general strategy for radical functionalization

• David T. Nemoto Jr,
• Kang-Jie Bian,
• Shih-Chieh Kao and
• Julian G. West

Beilstein J. Org. Chem. 2023, 19, 1225–1233, doi:10.3762/bjoc.19.90

• . Further, we demonstrated that diazidation could be rendered catalytic using Fe(III) nitrate hydrate III as the iron source and performing the reaction under continuous flow conditions. Interestingly, this mechanism bears some similarity to Lin’s electrocatalytic diazidation, where azido radical generation

Selective and scalable oxygenation of heteroatoms using the elements of nature: air, water, and light

• Damiano Diprima,
• Hannes Gemoets,
• Stefano Bonciolini and
• Koen Van Aken

Beilstein J. Org. Chem. 2023, 19, 1146–1154, doi:10.3762/bjoc.19.82

• additional reaction pathway is proposed in which the incorporated oxygen on the heteroatoms originates from water. Furthermore, the addition of certain additives enhances productivity by affecting kinetics. The industrial potential is demonstrated by conveniently transferring the batch protocol to continuous

• running the process in continuous flow [5][6][7][8]. Moreover, flow reactors that provide intense mixing can overcome the gas–liquid mass transfer limitations typical of batch reactions and improve productivity. Several studies have demonstrated the scalability and safety of such methods for the oxidation

• of water (Table 1, entries 1 and 2), the addition of oxygen (entries 1, 5, and 6) and light in the UV-A region (entries 8 and 9) turned out to be crucial (see Supporting Information File 1, Table S2). Additives With the ultimate goal in mind to develop a safe and scalable protocol in continuous flow

Photoredox catalysis harvesting multiple photon or electrochemical energies

• Mattia Lepori,
• Simon Schmid and
• Joshua P. Barham

Beilstein J. Org. Chem. 2023, 19, 1055–1145, doi:10.3762/bjoc.19.81

• feedstocks, and scalability up to gram scales in continuous flow. This review provides comparisons between the two techniques (multi-photon photoredox catalysis and PEC) to help the reader to fully understand their similarities, differences and potential applications and to therefore choose which method is

• first efforts in this direction [32][33]. Finally, both techniques are amenable to large-scale synthesis and ideally integrated with state-of-the-art reactor technology platforms, such as continuous flow reactors and high throughput screening plates. Various examples of scalability will be highlighted

• indoline scaffolds (22a,b) via a radical-polar crossover mechanism (Figure 12C) [65], showcasing the power of conPET in dearomatization reactions. Finally, the synthesis of tetraphenylphosphonium chloride (20a) could be scaled up efficiently in an operationally very simple continuous-flow setup with only